"CHAPTER 24 GENETICS AND GENOMICS"
CHAPTER 24: GENETICS AND GENOMICS LEARNING OUTCOMES: 24.1 Introduction 1. Distinguish among genome, gene, and chromosome. 2. Define genetics. 3. Explain how genetic information passes from generation to generation. 4. Explain how the human genome is an economical storehouse of information. 24.2 Modes of Inheritance 5. State the two bases of genetic predictions. 6. Define the two types of chromosomes. 7. Explain the basis of multiple alleles of a gene. 8. Distinguish between heterozygous and homozygous; genotype and phenotype; dominant and recessive. 9. Distinguish between autosomal recessive and autosomal dominant inheritance. 24.3 Factors That Affect Expression of Single Genes 10. Explain how and why the same genotype can have different phenotypes among individuals. 24.4 Multifactorial Traits 11. Describe how traits determined by genes and the environment are inherited. 24.5 Matters of Sex 12. Describe how and when sex is determined. 13. Explain how X-linked inheritance differs from inheritance of autosomal traits. 14. Discuss factors that affect how phenotypes may differ between the sexes. 24-1 CHAPTER 24: GENETICS AND GENOMICS LEARNING OUTCOMES: 24.6 Chromosome Disorders 15. Describe three ways that chromosomes can be abnormal. 16. Explain how prenatal tests provide information about chromosomes. 24.7 Gene Expression Explains Aspects of Anatomy and Physiology 17. Describe what type of information gene expression profiling provides. 18. Explain how a DNA microarray works. 24-2 CHAPTER 24: GENETICS AND GENOMICS 24.1 INTRODUCTION A. Genetics is the study of inheritance of characteristics and human variability. B. The human genome is comprised of 24,000 protein-encoding genes. 1. Genes are composed of DNA and are held on chromosomes. 2. The human genome is an economical information store because RNA molecules can represent parts of these 24,000 genes, and as result produce 100, 000-200,000 different proteins. 3. Genetic change drives evolution. a. Genetic errors may also lead to disease. 4. Genetic information functions at several levels, including biochemical, cell, tissue, individual, and population levels. 5. Genomics is the science which looks at the human body in terms of multiple, interacting genes, whose expression also responds to environmental influences. a. Gene expression patterns reveal the identities and civilities of proteins in cells = Proteomics, which can explain physiological processes. B. GENETICS BACKGROUND 1. Genetics is the study of INHERITANCE of characteristics and human VARIABILITY. a. The term "genetics" is derived from the word "GENE". b. A gene codes for a particular heritable trait (or protein). o i.e. blood type, hair color, eye color etc. c. Genes are carried on CHROMOSOMES that are composed of DNA (Deoxyribonucleic acid). See Fig 24.1, page 918. d. A GENE (composed of DNA) is the portion of a chromosome that codes for a particular heritable trait (or protein). e. More specifically, GENES TELL OUR CELLS WHICH PROTEINS TO MAKE. o Proteins have many important functions!!!! 1. structure (Example = _____________________) 2. transport (Example = _____________________) 3. movement (Example = _____________________) 4. chemical messengers (Example = _____________) 5. defense (Example = _____________________) 6. ENZYMES. f. In other words, our DNA holds the code for every protein that makes us and allows us to function! 24-3 CHAPTER 24: GENETICS AND GENOMICS 24.1 INTRODUCTION B. GENETICS BACKGROUND 2. Gene Mutations a. If there is an error in the DNA code (i.e. in a gene), this is called a MUTATION. o If a mutation occurs in a gene, the end-product, the protein will be altered or absent: 1. An enzyme may not be made at all. See Fig 4.26, page 138. E1 E2 E3 E4 A B C D E When an enzyme is lacking from a metabolic pathway, childhood storage diseases result. Examples include Tay-Sachs, PKU, Niemen-Pick's. 2. A protein may have altered function. See Fig 24.2, page 919. Examples include cystic fibrosis & sickle-cell anemia 3. A protein may be produced in excess. In epilepsy, where excess GABA leads to excess norepinephrine. 3. How Genes are Transferred to Offspring (Review from chapter 22) a. The genetic information of living organisms is DNA (deoxyribonucleic acid) that is carried on the genes of chromosomes. b. In humans, each somatic (body) cell is diploid, which means the cell contains 46 chromosomes or 23 pairs. c. Human sex cells or gametes, however, are haploid, which means the cell contains only 23 chromosomes. d. Meiosis is the type of cell division that results in gametes that possess half the chromosome number of the parent cell (i.e. meiosis reduces the chromosome number by one-half). o Male sperm (haploid) = 23 chromosomes (1 set) o Female egg (haploid) = 23 chromosomes (1 set) o Fertilization results is zygote (diploid) = 46 chromosome (2 sets). 24-4 CHAPTER 24: GENETICS AND GENOMICS 24.1 INTRODUCTION B. GENETICS BACKGROUND 4. Development following Fertilization a. The zygote formed by fertilization will divide into 2, 4, 8, 16, 32, 64 ... billions of cells to make up a human organism, however the DNA/genes/chromosomes will be identical in every one of those billion cells. b. If a mutation exists in the zygote, it will also be in every one of those billion cells in the human organism. c. If a problem occurs during meiosis, a sperm or egg may have too many or too few chromosomes, and result in a zygote with more or less than 46 chromosomes: o 24 egg + 23 sperm = 47 chromosome zygote 1. Down's (trisomy 21) 2. Patau's (trisomy 13) 3. Edward's (trisomy 18 ) o 23 egg + 22 sperm = 45 chromosome zygote 1. Turner Syndrome 24.2 MODES OF INHERITANCE: A. Chromosomes and Genes Come in Pairs 1. As humans, most of our body cells contain 46 chromosomes or two pairs: a. 23 (or 1 set) from mom b. 23 (or 1 set) from dad 2. A map of these chromosomes is called a karyotype. See Fig 24.3, page 920. a. Our chromosomes are paired. o homologous chromosomes b. We possess 22 homologous pairs of autosomes. o These chromosomes carry the genes for most of our traits (proteins). c. We possess 1 pair of sex chromosomes. o Females have a homologous XX pair. o Males have a non-homologous XY pair. See Fig 24.11, page 927. 24-5 CHAPTER 24: GENETICS AND GENOMICS 24.2 MODES OF INHERITANCE: A. Chromosomes and Genes Come in Pairs 3. The karyotype of a fetus can be obtained by a prenatal test called an amniocentesis where many chromosomal abnormalities can be detected. 4. A gene codes for a heritable trait (or protein). a. hair color b. eye color c. blood type 5. Alleles are alternate forms of genes. a. The gene for eye color has several alleles. Two major alleles are: o brown o blue b. Some alleles are dominant over others. o Brown is dominant over blue. 1. The dominant allele brown is written as an upper case letter (B) 2. The recessive allele blue is written as a lower case letter (b). c. We inherit one (1) allele of a gene from each parent and therefore have two (2) alleles for each gene. o If we inherit identical alleles, we are said to be homozygous for the trait. 1. BB = homozygous dominant 2. bb = homozygous recessive o If we inherit two different alleles, we are said to be heterozygous for the trait. 1. Bb = heterozygous. 6. PHENOTYPE VS. GENOTYPE a. The phenotype is the expressed trait. o brown eyes o blue eyes b. The genotype is the genetic makeup of the trait. o BB or homozygous dominant o Bb or heterozygous 24-6 CHAPTER 24: GENETICS AND GENOMICS 24.2 MODES OF INHERITANCE B. Dominant and Recessive Inheritance Practice Problems 1. If brown eyes are dominant over blue eyes, predict the offspring of a cross between two individuals who are heterozygous for eye color. a. Interpret given information: What are the genotypes and resulting cross of these two individuals? o Brown = B; Blue = b. o Individual 1 =_______(Bb); Individual 2 = _____(Bb). o Therefore cross would be _______ x _______. (Bb x Bb) b. What allele(s) would be present in each of the individuals' sex cells? o Individual 1 = ½ ____(B) & ½ _____(b) o Individual 2 = ½ ____(B) & ½ _____(b). c. Set up a Punnett Square illustrating the possible crosses B b B BB Bb b Bb bb d. Interpret the results of the cross: o The genotypic ratio would be: 1. one (1) homozygous dominant (BB) individual : 2. two (2) heterozygous (Bb) individuals : 3. one (1) homozygous recessive (bb) individual. o The phenotypic ratio would be: 1. three (3) individual with brown eyes: 2. one (1) individual with blue eyes. 24-7 CHAPTER 24: GENETICS AND GENOMICS 24.2 MODES OF INHERITANCE B. Dominant and Recessive Inheritance Practice Problems 2. In humans, widow's peak is dominant over straight hairline. Predict the offspring of the cross between an individual who is homozygous dominant for hairline, with an individual who is homozygous recessive for hairline. a. Interpret given information: o Widow’s peak = W; Straight hairline = w. o Therefore the cross is: _________ x ___________. (WW) (ww) b. Determine alleles in sex cells: o All of WW’s alleles would be _______(W) o All of ww’s alleles would be _______ (w). c. Set up a Punnett Square: W W w Ww Ww w Ww Ww d. Interpret results: o Genotypic Ratio: All individuals are heterozygous for hairline. o Phenotypic Ratio: All individuals have widow’s peaks. 24-8 CHAPTER 24: GENETICS AND GENOMICS 24.2 MODES OF INHERITANCE C. Major Modes of Inheritance 1. Introduction: a. Whether a trait is dominant or recessive, autosomal or sex-linked is called its mode of inheritance. b. The mode of inheritance has important consequences in predicting the chance that offspring will inherit an illness or trait. c. Three important rules exist: 1. Autosomal Conditions are equally likely to affect both sexes. ○ Sex-linked characteristics affect males much more often than females. 2. Recessive conditions are usually inherited from two healthy heterozygous parents (carriers). ○ Recessive conditions "skip" generations. 3. Dominant conditions are inherited by at least one affected parent. ○ Dominant conditions do not skip generations. 2. The major modes of inheritance include autosomal recessive (AR), autosomal dominant (AD), incomplete dominance, codominance, and sex-linked (discussed in 24.5 below). a. Autosomal Recessive (AR) Inheritance Example Using Cystic Fibrosis: See Fig 24.4, page 921. o Both parents are heterozygous carriers (i.e. they have one normal (wild type) & one mutant allele); genotype is( + , cf) o What alleles would be present in the female’s eggs? 1/2 = ________(+) , 1/2 = _________(cf) o What alleles would be present in the male’s sperm? 1/2 = ________(+) , 1/2 = _________(cf) o What are the chances that parents who are heterozygous for cf will have an afflicted child? + Cf + ++ + cf cf + cf cf cf ○ Results: These parents have 1. ____% (1/4) chance of having a normal child (+,+) 2. ____% (½) chance of having a child who is carrier of CF (+, cf) 3. ____% (1/4) chance of having a child with CF (cf, cf). 24-9 CHAPTER 24: GENETICS AND GENOMICS 24.2 MODES OF INHERITANCE C. Major Modes of Inheritance 2. b. Autosomal Dominant Inheritance Example using Huntington Disease: See Fig 24.5, page 921. o Parents' genotypes? 1. Affected parent = + , HD 2. Unaffected parent = +,+ o Alleles or Sex cells? 1. Affected parent: ½_____ (+), ½ _____ (HD) 2. Unaffected parent: ½ _____ (+), ½ _____ (+). o What are the chances that a male who carries the Huntington gene & a normal female will have an afflicted child? + HD + ++ + HD + ++ + HD o Results: These parents have the chance of having 1. _____% (½) their offspring that carry the allele for Huntington disease and therefore those children will develop the disease during mid-life and 2. ______% (½) their offspring who do not carry the HD allele and therefore will be normal. 24-10 CHAPTER 24: GENETICS AND GENOMICS 24.2 MODES OF INHERITANCE C. Major Modes of Inheritance 2. c. Incomplete Dominant Inheritance. o The heterozygous (carrier) parents express a moderate form of the disease called sickle cell trait. ○ Sickle Cell Anemia (or disease) is an example, in which one of the four amino acid chains in hemoglobin is incorrect causing sickling of erythrocytes. o What are the chances that a male with sickle cell trait and a normal female will have an afflicted child, either with sickle cell anemia or sickle cell trait? o Male: HbA, HbS Female: HbA, HbA o Sperm: 1/2 = ______( HbA), 1/2 = ______( HbS) Eggs: 1/2 = ______( HbA), 1/2 = ______( HbA) o Punnett Square: HbA HbS HbA HbA HbA HbA HbS HbA HbA HbA HbA HbS o Results: These parents have the chance of having 1. _____% (½) their offspring that carry sickle cell trait, 2. _____% (½) their offspring of being normal. ○ Also see Fig 24.6, page 922, which illustrates incomplete inheritance involved in plasma cholesterol levels. d. Codominant Inheritance o Results when both alleles are equally expressed o Example is AB blood type. 24-11 CHAPTER 24: GENETICS AND GENOMICS 24.3 FACTORS THAT AFFECT EXPRESSION OF SINGLE GENES A. Introduction: 1. Most genotypes vary somewhat from person to person, due to the effects of the environment and other genes. a. Even identical twins may not exhibit the same symptoms of an inherited illness in exactly the same way. b. The terms penetrance, expressivity, and pleiotropy are used to describe these distinctions of genotype. B. Penetrance and Expressivity 1. Penetrance a. Is an all-or-none phenotypic presentation of a genotype. o Whether or not the allele is exhibited in phenotype. b. Completely penetrant = all who have allele, exhibit trait. c. Incompletely penetrant = only some with allele, show trait. o Polydactyly is an example, where some people who inherit the allele have extra digits, but others known to have the allele have the normal 10 fingers and 10 toes. o Incomplete penetrance is difficult to calculate in a population, however if 50 of 100 individuals who have the allele exhibit the trait, then numerically = 50% penetrance. 2. Expressivity a. Is how much the phenotype is expressed or the severity of the expressed phenotype. b. Sometimes variable intensity is seen among people who do exhibit the trait. o For example some people with polydactyly have 1 extra digit on both hands and one foot o another may have two extra digits on both hands and feet o another may just have an extra fingertip. * Polydactyly is both incomplete penetrant and variably expressive. C. Pleiotropy 1. A phenomenon when a single genetic disorder can produce several symptoms. (i.e. when a single genotype, produces many phenotypes) 2. Seen in genetic diseases that affect a single protein in different body locations. 3. Example is autosomal dominant defect of elastic connective tissue called fibrillin in Marfan Syndrome. Fibrillin is abundant in many tissues: a. Lens of eye (causing lens dislocation) b. Bones of limbs, fingers and ribs (causing long limbs and spindly fingers) c. AORTA (causing weakening which may result in sudden death fatal aneurysm if not detected, and surgically repaired). 4. Another example is porphyria variegata. See Clinical Application 14.1, page 530. 24-12 CHAPTER 24: GENETICS AND GENOMICS 24.3 FACTORS THAT AFFECT EXPRESSION OF SINGLE GENES D. Genetic Heterogeneity 1. When more that one genotype causes the same phenotype a. Nearly 200 forms of hereditary deafness are each due to impaired actions of a different gene. o Different genes affect different aspects of hearing 2. Can occur for genes that encode different enzymes within the same metabolic pathway. a. Eleven biochemical reactions lead to blood clotting. b. Clotting disorders may result from mutations in genes (genotype) that encode for any one of those 11 enzymes, however all individuals who exhibit the trait have the same symptoms of bleeding (phenotype). 24.4 MULTIFACTORAL TRAITS A. Polygenic Traits 1. Determined by more than one gene. 2. Height, skin color, eye color are polygenic traits. a. Figure 24.8, page 925, which illustrates variations in skin color using a model of three genes. b. Figure 24.9, page 926, which illustrates variations in eye color using a model of two genes with two alleles each. B. Multifactorial Traits 1. Determined by more than one gene (polygenic) and environment. 2. Height is multifactorial because it is polygenic plus nutrition plays a role. 3. Figure 24.7, page 925, which illustrates the continuously varying nature of height. 24-13 CHAPTER 24: GENETICS AND GENOMICS 24.5 MATTERS OF SEX A. Sex Determination: See Fig 24.10, page 927. 1. In sexually reproducing animals, two types of chromosomes exist. a. Most pairs are called autosomes which determine most traits. b. One pair represents the sex chromosomes, which determine sex of the individual. o Female = XX o Male = XY. See Fig 24.11, page 927. 2. Following gametogenesis (sex cell formation meiosis): a. In females, the ova (gametes) contain 22 autosomes and the X sex chromosome. All ova contain the X chromosome. XX X (ova) b. In males, the sperm contain 22 autosomes, but o half the sperm carry the X sex chromosome and o the other half of the sperm contain the Y sex chromosome. XY X or Y (sperm) c. During fertilization, the chance of: o an X sperm & the X ova fusing to produce a female (XX) is 50% o a Y sperm & the X ova fusing to produce a male (XY) is 50%. 24-14 CHAPTER 24: GENETICS AND GENOMICS 24.5 MATTERS OF SEX B. Sex Chromosomes and Their Genes 1. Sex-linked Inheritance a. Traits transmitted on the X chromosome are said to be sex-linked (or X-linked). b. Males need only one copy of a mutant allele to possess the disorder XaY. c. Females need two copies of the mutant allele to be affected (XaXa), however if they have one mutant allele, they are carriers of the disease (XaX0). d. Example of X-linked inherited disease is Hemophilia, in which a clotting factor is missing that leads to bleeding disorders. e. What are the chances that a female hemophilia carrier and normal male will have a child afflicted with the disease? o Genotypes of parents: 1. Female = XHXh 2. Male = XhY. o Alleles of parents: 1. Female’s are ½ XH and ½ Xh 2. Males are ½ Xh and ½ Y. o Punnett square: XH Xh Xh XH Xh Xh Xh Y XHY Xh Y o Results: These parents have the chance of having 1. ____% (½) their female offspring as hemophilia carriers and 2. _____% (½) their female offspring as normal, and the chance of having 3. _____% (½) of their male offspring afflicted with hemophilia and 4. ______% (½) their male offspring as normal. 24-15 CHAPTER 24: GENETICS AND GENOMICS 24.5 MATTERS OF SEX C. Gender Effects on Phenotype 1. Introduction: certain autosomal traits are expressed differently in males and females, due to difference between the sexes. 2. Sex-limited Traits a. Tend to affect only one of the sexes. b. Reason that a woman doesn’t grow a thick beard, but she passes genes to her sons that specify heavy beard growth. c. In animal breeding, milk yield and horn development are important sex-limited traits. 3. Sex-influenced Traits a. Traits that are dominant in one sex but recessive in the other b. Due to hormonal differences c. Reason that more men are bald than women. o Heterozygous males are bald. o Heterozygous females are not bald. 1. Females must have two mutant alleles to be bald. 24.6 CHROMOSOME DISORDERS A. Introduction 1. Missing, extra and rearranged chromosomes or chromosome pieces can cause syndromes with specific sets of characteristics. These syndromes may cause either: a. an imbalance of genetic information or b. disrupt a vital gene B. Polyploidy = an extra set of chromosomes 1. results from fertilization in which one gamete is diploid 2. Triploid = three sets of chromosomes or 69 (rather than 46) . a. results in death as embryo or fetus b. Live births only survive a few days. 24-16 CHAPTER 24: GENETICS AND GENOMICS 24.6 CHROMOSOME DISORDERS C. Aneuploidy = missing one or having one extra chromosome. 1. Results from non-disjunction during either Meiosis I or Meiosis II, producing a gamete with either a missing or extra chromosome. a. See Figure 24.12, page 930. 2. At fertilization, a monosomic or trisomic zygote results. a. Individuals with trisomies are more likely to survive to be born than those with monosomies. o 24 egg + 23 sperm = 47 chromosome zygote 1. Trisomy 21 = Down Syndrome: See Clinical Application 24.2 on page 931. ○ Likelihood of giving birth to a child with Down's increases drastically with maternal age. See Table 24A, page 931. 2. Patau's (trisomy 13) 3. Edward's (trisomy 18 ) o 23 egg + 22 sperm = 45 chromosome zygote 1. Turner Syndrome. D. PRENATAL GENETIC TESTING See Fig 24.13, page 932 and Table 24.2, page 933. 1. Ultrasound a. can detect large-scale structural abnormalities and assess growth 2. Maternal Serum Markers a. indirectly detects small fetal liver, which may indicate a trisomy 3. AMNIOCENTESIS a. indicated in women over the age of 35 who have already given birth to a child with a chromosomal abnormality or whose family history (paternal included) shows any sign of genetic disease b. Performed after 14th week gestation, when needle is inserted into amniotic sac and 5ml of fluid containing fetal cells is extracted. c. Cells are analyzed by karyotyping. o Useful in detecting many genetic disorders. o 0.5% chance of miscarriage 4. CHORIONIC VILLUS SAMPLING a. Indications same as above b. performed as early as 8 weeks gestation c. 1-2% spontaneous abortion rate 5. FETAL CELL SORTING a. Involves obtaining and analyzing rare fetal cells in maternal circulation. b. These cells may be responsible for autoimmune disorders including scleroderma (see Chapter 16). 24-17 CHAPTER 24: GENETICS AND GENOMICS 24.7 GENE EXPRESSION EXPLAINS ASPECTS OF ANATOMY AND PHYSIOLOGY A. The human genome is comprised of 24,000 protein-encoding genes. 1. The human genome is an economical information store because RNA molecules can represent parts of these 24,000 genes, and as result produce 100, 000-200,000 different proteins. 2. Genomics is the science which looks at the human body in terms of multiple, interacting genes, whose expression also responds to environmental influences. a. Gene expression patterns reveal the identities and activities of proteins in cells = Proteomics. ○ Proteomics can explain physiological processes. b. DNA Microarrays are used to monitor gene expression. Fig 24.15, page 934, DNA Microarrays. c. Comparing gene expression profiles for the same cell type under different conditions can provide information on disease. Other Interesting Topics: A. Direct-To-Consumer Genetic Testing. See introduction on page 917. B. Genetic Counselors Communicate Modes of Inheritance. See Clinical Application 24.1, page 923. C. Gene Therapy. See box on page 933. CHAPTER SUMMARY – see pages 935-936. CHAPTER ASSESSMENTS – see page 936-937. INTEGRATIVE ASSESSMENTS/ CRITICAL THINKING – see page 937-938. 24-18